Topic Highlight
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jan 7, 2007; 13(1): 104-124
Published online Jan 7, 2007. doi: 10.3748/wjg.v13.i1.104
The woodchuck as an animal model for pathogenesis and therapy of chronic hepatitis B virus infection
Stephan Menne, Paul J Cote
Stephan Menne, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States
Paul J Cote, Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC, United States
Author contributions: All authors contributed equally to the work.
Supported by contract N01-AI-05399 to the College of Veterinary Medicine, Cornell University from the National Institute of Allergy and Infectious Diseases. PC and SM also have been supported by contract N01-AI-95390 to the Georgetown University Medical Center, Georgetown University from the National Institute of Allergy and Infectious Diseases
Correspondence to: Stephan Menne, PhD, Department of Clinical Sciences, College of Veterinary Medicine, Veterinary Medical Center, Cornell University, Ithaca, New York 14853, United States.
Telephone: +1-607-2533280 Fax: +1-607-2533289
Received: July 28, 2006
Revised: August 25, 2006
Accepted: October 4, 2006
Published online: January 7, 2007

This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined WHV inocula, have enhanced our understanding of the virology and immunology of HBV infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and of viral load on the natural history of infection and disease progression has been firmly established along the way. More recently, the model has shed new light on the role of host immune responses in these natural processes, and on how the immune system of the chronic carrier can be manipulated therapeutically to reduce or delay serious disease sequelae through induction of the recovery phenotype. The woodchuck is an outbred species and is not well defined immunologically due to a limitation of available host markers. However, the recent development of several key host response assays for woodchucks provides experimental opportunities for further mechanistic studies of outcome predictors in neonatal- and adult-acquired infections. Understanding the virological and immunological mechanisms responsible for resolution of self-limited infection, and for the onset and maintenance of chronic infection, will greatly facilitate the development of successful strategies for the therapeutic eradication of established chronic HBV infection. Likewise, the results of drug efficacy and toxicity studies in the chronic carrier woodchucks are predictive for responses of patients chronically infected with HBV. Therefore, chronic WHV carrier woodchucks provide a well-characterized mammalian model for preclinical evaluation of the safety and efficacy of drug candidates, experimental therapeutic vaccines, and immunomodulators for the treatment and prevention of HBV disease sequelae.

Keywords: Woodchuck, Woodchuck hepatitis virus, Hepatitis B virus, Neonatal-acquired infection, Adult-acquired infection, Resolution, Chronicity, Humoral immune response, Cellular immune response, Antiviral therapy, Immunotherapy, Combination therapy, Hepatocellular carcinoma